Aims. We search for muon neutrinos in coincidence with GRBs with the ANTARES neutrino detector using data from the end of 2007 to 2011. Methods. Expected neutrino fluxes were calculated for each ...burst individually. The most recent numerical calculations of the spectra using the NeuCosmA code were employed, which include Monte Carlo simulations of the full underlying photohadronic interaction processes. The discovery probability for a selection of 296 GRBs in the given period was optimised using an extended maximum-likelihood strategy. Results. No significant excess over background is found in the data, and 90% confidence level upper limits are placed on the total expected flux according to the model.
Several studies have reported on an association between hepatitis C virus (HCV) antibody status and the development of chronic kidney disease (CKD), but the role of HCV viremia and genotype are not ...well defined.
Patients with at least three serum creatinine measurements after 1 January 2004 and known HCV antibody status were included. Baseline was defined as the first eligible estimated glomerular filtration rate (eGFR) (Cockcroft-Gault equation), and CKD was either a confirmed (>3 months apart) eGFR of 60 ml/min per 1.73 m or less for patients with a baseline eGFR more than 60 ml/min per 1.73 m or a confirmed 25% decline in eGFR for patients with a baseline eGFR of 60 ml/min per 1.73 m or less. Incidence rates of CKD were compared between HCV groups (anti-HCV-negative, anti-HCV-positive with or without viremia) using Poisson regression.
Of 8235 patients with known anti-HCV status, 2052 (24.9%) were anti-HCV-positive of whom 983 (47.9%) were HCV-RNA-positive, 193 (9.4%) HCV-RNA-negative and 876 (42.7%) had unknown HCV-RNA. At baseline, the median eGFR was 97.6 (interquartile range 83.8-113.0) ml/min per 1.73 m. During 36123 person-years of follow-up (PYFU), 495 patients progressed to CKD (6.0%) with an incidence rate of 14.5 per 1000 PYFU (95% confidence interval 12.5-14.9). In a multivariate Poisson model, patients who were anti-HCV-positive with HCV viremia had a higher incidence rate of CKD, whereas patients with cleared HCV infection had a similar incidence rate of CKD compared with anti-HCV-negative patients. There was no association between CKD and HCV genotype.
Compared with HIV-monoinfected patients, HIV-positive patients with chronic rather than cleared HCV infection were at increased risk of developing CKD, suggesting a contribution from active HCV infection toward the pathogenesis of CKD.
Abstract Objectives The relation between C-Reactive Protein (CRP), depression and antidepressant consumption has been well explored in major depressive disorders but not in schizophrenia, which has a ...high rate of depression comorbidity. The objectives of this study were: (i) to determine the prevalence of abnormal CRP levels, depression and antidepressant consumption in a multicenter community-dwelling sample of subjects with schizophrenia (ii) to determine the association between abnormal CRP levels, depression and antidepressant consumption in schizophrenia. Method 219 stable patients with schizophrenia (mean age=31.6 years, 75.3% male gender) were systematically included in the multicentre network of FondaMental Expert Center for schizophrenia (FACE-SZ) and assessed with a dedicated electronic medical record including the Structured Clinical Interview for DSM-IV Axis I Disorders and Calgary Depression Scale for depression. High sensitivity CRP (hs-CRP) was measured with an assay using nephelometry (Dade Behring). Abnormal CRP level was defined by levels >3 mg/L. Current medication was recorded. Results Overall, 63 subjects (28.8%) were found to have abnormal CRP levels, 43 (20.1%) received a diagnosis of comorbid current depression, and 51 (31.9%) had ongoing antidepressant treatment. In univariate analysis, abnormal CRP levels were found to be significantly associated with body mass index (BMI) ( p <0.0001), hypertriglyceridemia ( p =0.0015), high waist circumference ( p <0.0001), metabolic syndrome ( p =0.0011), abdominal obesity ( p <0.0001) and with antidepressant consumption ( p =0.01), while depression, psychotic symptomatology, age of onset, illness duration, sociodemographic characteristics, current tobacco or cannabis status, hypertension or high fasting glucose were not (all p >0.05). In a multivariate model, abnormal CRP was associated with antidepressant consumption independently of other confounding variables (adjusted Odds Ratio=2.8, 95% confidence interval 1.22–6.62). Metabolic syndrome was also independently associated with abnormal CRP (adjusted Odds Ratio=2.6, 95% confidence interval 1.01–6.71). Conclusion Abnormal CRP levels in schizophrenia were found to be associated with antidepressant consumption, but not with depression. The potential mechanisms were discussed. Antidepressant consumption should be systematically recorded in future studies exploring inflammation in schizophrenia. Future clinical trials of interventions directed at lowering the level of CRP and other inflammatory markers are discussed.
Atmospheric neutrinos are produced during cascades initiated by the interaction of primary cosmic rays with air nuclei. In this paper, a measurement of the atmospheric
energy spectrum in the energy ...range 0.1–200 TeV is presented, using data collected by the ANTARES underwater neutrino telescope from 2008 to 2011. Overall, the measured flux is ∼25 % higher than predicted by the conventional neutrino flux, and compatible with the measurements reported in ice. The flux is compatible with a single power-law dependence with spectral index
γ
meas
=3.58±0.12. With the present statistics the contribution of prompt neutrinos cannot be established.
To compare the incidence of dyslipidemia in people with HIV receiving integrase inhibitors (INSTI) versus boosted protease inhibitors (PI/b) and nonnucleoside reverse transcriptase inhibitors (NNRTI) ...within RESPOND consortium of prospective cohorts.
Participants were eligible if they were at least 18 years, without dyslipidemia and initiated or switched to a three-drug antiretroviral therapy (ART)-regimen consisting of either INSTI, NNRTI, or PI/b for the first time, between 1 January 2012 and 31 December 2018. Dyslipidemia was defined as random total cholesterol more than 240 mg/dl, HDL less than 35 mg/dl, triglyceride more than 200 mg/dl, or initiation of lipid-lowering therapy. Poisson regression was used to determine the adjusted incidence rate ratios. Follow-up was censored after 3 years or upon ART-regimen discontinuation or last lipid measurement or 31 December 2019, whichever occurred first.
Overall, 4577 people with HIV were eligible (INSTI = 66.9%, PI/b = 12.5%, and NNRTI = 20.6%), 1938 (42.3%) of whom were ART-naive. During 1.7 (interquartile range, 0.6-3.0) median years of follow-up, 1460 participants developed dyslipidemia incidence rate: 191.6 per 1000 person-years, 95% confidence interval (CI) 182.0-201.7. Participants taking INSTI had a lower incidence of dyslipidemia compared with those on PI/b (adjusted incidence rate ratio 0.71; CI 0.59-0.85), but higher rate compared with those on NNRTI (1.35; CI 1.15-1.58). Compared with dolutegravir, the incidence of dyslipidemia was higher with elvitegravir/cobicistat (1.20; CI 1.00-1.43) and raltegravir (1.24; CI 1.02-1.51), but lower with rilpivirine (0.77; CI 0.63-0.94).
In this large consortium of heterogeneous cohorts, dyslipidemia was less common with INSTI than with PI/b. Compared with dolutegravir, dyslipidemia was more common with elvitegravir/cobicistat and raltegravir, but less common with rilpivirine.
Objectives
Although direct‐acting antivirals (DAAs) can clear HCV in nearly all HIV/HCV‐coinfected individuals, high rates of reinfection may hamper efforts to eliminate HCV in this population. We ...investigated reinfection after sustained virological response (SVR) in HIV/HCV‐coinfected individuals in Europe.
Methods
Factors associated with odds of reinfection by 2 years after SVR in EuroSIDA participants with one or more HCV‐RNA test and 2 years follow‐up were assessed using logistic regression.
Results
Overall, 1022 individuals were included. The median age was 50 (interquartile range: 43–54 years), and most were male (78%), injection drug users (52%), and received interferon (IFN)‐free DAAs (62%). By 24 months, 75 7.3%, 95% confidence interval (CI): 5.7–8.9% individuals were reinfected. Among individuals treated prior to 2014, 16.1% were reinfected compared with 4.2% and 8.3%, respectively, among those treated during or after 2014 with IFN‐free and IFN‐based therapy. After adjustment, individuals who had started treatment during or after 2014 with IFN‐free or IFN‐based therapy had significantly lower odds of reinfection (adjusted odds ratio = 0.21, 95% CI: 0.11–0.38; 0.43, 95% CI: 0.22–0.83) compared with those who had received therapy before 2014. There were no significant differences in odds of reinfection according to age, gender, European region, HIV transmission risk group or liver fibrosis.
Conclusions
Among HIV/HCV‐coinfected individuals in Europe, 7.3% were reinfected with HCV within 24 months of achieving SVR, with evidence suggesting that this is decreasing over time and with use of newer HCV regimens. Harm reduction to reduce reinfection and surveillance to detect early reinfection with an offer of treatment are essential to eliminate HCV.
The ANTARES experiment consists of an array of photomultipliers distributed along 12 lines and located deep underwater in the Mediterranean Sea. It searches for astrophysical neutrinos collecting the ...Cherenkov light induced by the charged particles, mainly muons, produced in neutrino interactions around the detector. Since at energies of ∼10 TeV the muon and the incident neutrino are almost collinear, it is possible to use the ANTARES detector as a neutrino telescope and identify a source of neutrinos in the sky starting from a precise reconstruction of the muon trajectory. To get this result, the arrival times of the Cherenkov photons must be accurately measured. A to perform time calibrations with the precision required to have optimal performances of the instrument is described. The reconstructed tracks of the atmospheric muons in the ANTARES detector are used to determine the relative time offsets between photomultipliers. Currently, this method is used to obtain the time calibration constants for photomultipliers on different lines at a precision level of 0.5 ns. It has also been validated for calibrating photomultipliers on the same line, using a system of LEDs and laser light devices.
Background. Calendar trends in virologic failure (VF) among human immunodeficiency virus (HIV)-infected patients can help to evaluate the performance of healthcare systems and the need for new ...antiretroviral therapy (ART). We examined the time trend in the rate of VF beyond 6 months of ART between 1997 and 2011 in France. Methods. We included patients from the French Hospital Database on HIV who received at least 6 months of ART. VF was defined as 2 consecutive plasma HIV-RNA values >500 copies/mL or as 1 value >500 copies/mL followed by a treatment switch. We adjusted for patients' characteristics by fitting a multivariable generalized estimating equation logistic regression model with an exchangeable covariance matrix. Results. A total of 81 738 patients were enrolled, and median follow-up was 112.4 months. Median CD4 count was 333 cells/μL, and 23% of patients had HIV infection classified as Centers for Disease Control and Prevention stage C. Overall, 29.3% of patients received single/dual-drug ART initially, and 45.4% of patients experienced at least 1 episode of VF during follow-up. The percentage of patients with VF fell from 61.5% in 1997–1998 to 9.7% in 2009–2011 (P < .0001). Factors associated with the lower frequency of VF were recent calendar period, a higher contemporary CD4 cell count, and first-line regimens based on nonnucleoside reverse transcriptase inhibitors or integrase inhibitors. Conclusions. The proportion of HIV-infected patients experiencing VF during routine care fell markedly between 1997 and 2009–2011, to only 9.7%. This was attributed to the advent of fully active and better-tolerated antiretroviral drugs, and to national guidelines recommending rapid management of VF after mid-2000.
Background. The extent to which mortality differs following individual acquired immunodeficiency syndrome (AIDS)-defining events (ADEs) has not been assessed among patients initiating combination ...antiretroviral therapy. Methods. We analyzed data from 31,620 patients with no prior ADEs who started combination antiretroviral therapy. Cox proportional hazards models were used to estimate mortality hazard ratios for each ADE that occurred in >50 patients, after stratification by cohort and adjustment for sex, HIV transmission group, number of antiretroviral drugs initiated, regimen, age, date of starting combination antiretroviral therapy, and CD4+ cell count and HIV RNA load at initiation of combination antiretroviral therapy. ADEs that occurred in <50 patients were grouped together to form a “rare ADEs” category. Results. During a median follow-up period of 43 months (interquartile range, 19–70 months), 2880 ADEs were diagnosed in 2262 patients; 1146 patients died. The most common ADEs were esophageal candidiasis (in 360 patients), Pneumocystis jiroveci pneumonia (320 patients), and Kaposi sarcoma (308 patients). The greatest mortality hazard ratio was associated with non-Hodgkin' lymphoma (hazard ratio, 17.59; 95% confidence interval, 13.84–22.35) and progressive multifocal leukoencephalopathy (hazard ratio, 10.0; 95% confidence interval, 6.70–14.92). Three groups of ADEs were identified on the basis of the ranked hazard ratios with bootstrapped confidence intervals: severe (non-Hodgkin' lymphoma and progressive multifocal leukoencephalopathy hazard ratio, 7.26; 95% confidence interval, 5.55–9.48), moderate (cryptococcosis, cerebral toxoplasmosis, AIDS dementia complex, disseminated Mycobacterium avium complex, and rare ADEs hazard ratio, 2.35; 95% confidence interval, 1.76–3.13), and mild (all other ADEs hazard ratio, 1.47; 95% confidence interval, 1.08–2.00). Conclusions. In the combination antiretroviral therapy era, mortality rates subsequent to an ADE depend on the specific diagnosis. The proposed classification of ADEs may be useful in clinical end point trials, prognostic studies, and patient management.
Interactions of a collection of monoclonal antibodies (mAbs) to the recombinant Nicotiana tabacumauxin-binding protein 1 (Nt-abp1) were extensively characterized using surface plasmon resonance. ...Dynamic interaction studies using combinations of Nt-abp1, synthetic peptides corresponding to conserved sequences within auxin-binding proteins, and the mAbs have shown that a number of the mAbs recognized discontinuous epitopes revealing the junction of distinct domains in the folded protein. In particular, the two putative auxin binding domains and the C terminus of the protein were shown to interact with each other in the folded protein. Using the auxin-induced electrical response of tobacco protoplasts as a functional assay, all the mAbs exhibited either auxin antagonist or hormonomimetic properties. These effects, measured for the first time in homologous conditions, confirm that Nt-abp1 is present at the plasma membrane and is involved in the activation of the auxin-dependent electrical response of tobacco protoplasts. Based on our surface plasmon resonance data, we propose that the key event leading to the activation of this auxin electrical response consists of a conformational change in Nt-abp1.
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